The nasal mucosa is the first internal surface to encounter aeroallergens, airborne pathogens, and airborne toxins. Analysis of nasal responses will likely provide insights into normal host defense mechanisms at the mucous membrane level. A guinea pig model of nasal responses was developed and was shown to resemble human cholinergic, histamine and neuropeptide responses. Guinea pigs were desensitized to capsaicin in order to allow examination of the contribution of sensory neuropeptides to nasal responses; histamine induced secretions were significantly reduced suggesting a role for neuropeptides in allergic reactions. The primary muscarinic receptor on human submucosal glands was determined to be of the M3 type, both by receptor analysis and by functional analysis. M3 mRNA was also localized to the glands. The primary enzymes involved in metabolizing the neuropeptides were characterized: neutral endopeptidase is found in the endothelium, epithelium and serous cells while angiotensin converting enzyme is in the interstitium. Proteases released from PMN might be capable of damaging the nasal epithelium. However, the serous cells were found to synthesize and secrete secretory leukoprotease inhibitor (SLPI). SLPI constitutes up to 3% of secreted protein and protects the nasal epithelium during infections. Rhinovirus is the most common virus to cause upper respiratory infections (URI). URI's are universally experienced infections causing rhinorrhea. The source of rhinorrhea during the initial phase of a URI in vascular bed due to increased vascular permeability. During the resolution phase of a URI, the source of secretions is glandular.